Although glycoproteins from Cystic Fibrosis (CF) patients have altered carbohydrate and sulfate composition as compared to controls, the functional significance of these observations to the pathology observed in CF is unknown. The underlying hypothesis of this project addresses this problem by proposing that "the coagulation of secretory material in the exocrine ducts of individuals with CF results from either an abnormal processing or an over-production of highly anionic glycoconjugates from the ductal epithelium which complexe with and precipitate the cationic exocrine glands." The studies proposed in this project will first determine if anionic glyco-conjugates and produced in CF fibroblasts and will then relate these observations to the synthesis and secretion of similar macromolecules in the ductal epithelium of an exocrine gland typically affected in this disease (the pancreas) by ultilizing the reserpinized rat as an animal model of CF. Specifically, lectins will be used as cell surface probes to quantitate differences in the carbohydrate composition of plasmalemmal glycoconjugates in normal and CF strains of human fibroblasts. In addition, the sulfate content of glycoproteins of normal and CF fibroblasts will also be analyzed. As differences in carbohydrate and sulfate composition are detected and quantitated, appropriate lectins can then be used as reagents to identify individual species of glycoproteins altered in CF fibroblasts using 2-D gel electrophoresis couplied with iodinated-lectin overlay techniques. Studies will then be conducted to analyze the synthesis and secretion of sulfated macromolecules (to include glycoconjugates) from the ductal epithelium of exocrine glands affected in CF. In initial studies, the synthesis and secretion of sulfated macromolecules from the epithelium of pancreatic ducts isolated from control and reserpine-treated rats (a proposed animal model of CF) will be analyzed using morphological and biochemical techniques. Future studies will then focus on other exocrine studies affected in CF and on secretory fluids obtained from CF patients.